High blood levels of a cell-regulating protein in patients with acute ischemic stroke can identify those with an increased risk of bleeding in the brain, according to a report in today’s rapid access issue of Stroke: Journal of the American Heart Association.
Identifying which patients are at risk for the bleeding – the most feared complication of clot-busting stroke therapy – can improve the risk-benefit ratio.
Researchers investigating the mechanisms behind such bleeding found high blood levels of a protein called cellular fibronectin (c-Fn) predicted bleeding risk.
“This study demonstrates that blood c-Fn levels are significantly higher in patients in whom bleeding develops after clot-busting therapy. Therefore it might be a useful marker of those patients who are at greatest risk of thrombolytic treatment,” said lead author Mar Castellanos, M.D., a neurologist at the Hospital Universitari Doctor Josep Trueta in Girona, Spain.
The results suggest that c-Fn levels of 3.6 micrograms per milliliter or greater can predict the development of bleeding with 100 percent accuracy.
The clot-busting drug tissue plasminogen activator (tPA) can reduce the severity of an ischemic stroke and thus, reduce debilitating effects. It is the only U.S. Food and Drug Administration-approved treatment for ischemic stroke and must be given within three hours of symptom onset.
However, tPA could also increase risk of bleeding in the brain. Evidence suggests that tPA may indirectly cause damage to the cells that line the inner walls of blood vessels.
Fibronectins promote cell-to-cell and other interactions. C-Fn is largely confined to the cells that line blood vessels, where it mediates the interactions between those cells and blood cells. It also plays an important role in blood-clot formation.
Castellanos and his colleagues studied 87 ischemic stroke patients (average age 67, 59 percent men) treated with intravenous tPA at two university hospitals in Spain within six hours after their symptoms began. Seventy-one were treated within three hours. Giving tPA within three hours is the time frame considered the most effective for treating ischemic stroke. Prior to tPA treatment, the researchers drew blood samples and did CT scans, which they examined to learn the amount of neurological injury already caused by the stroke.
In their study, the researchers looked for hemorrhagic transformation – the point when damaged brain tissue begins to leak blood. Twenty-six (30 percent) of the patients developed bleeding. Blood levels of c-Fn before tPA-administration were significantly higher in patients with hemorrhagic transformation (4.8 micrograms per milliliter) than those who did not develop bleeding (1.7 ug/mL).
The greater the severity of the bleeding, the higher the levels of c-Fn, researchers said.
Among the study’s other findings: